1. Field of Invention
The present invention generally relates to a method and system for the easy identification and culling of one or more of a plurality of encoded objects that are each associated with an individual retention position on a holding means or a rack, and for re-association of each encoded object with a new retention position if such encoded object is moved. More specifically, the present invention describes in one embodiment a method and a system which assists in the culling of encoded objects on the entire rack of encoded objects using a scan-readable symbology which is continuously updated (in real time). The method and system of the present invention presents a graphical interface representative of the position of each encoded object in a multi-well rack, and of information pertaining to properties of the materials stored within such object.
2. Discussion of Related Art
Research in the biological and chemical fields has dramatically changed in a short few years from predominantly manually-based assay methodologies and synthesis protocols to nearly fully-automated assays and protocols. The automation of biological and chemical processes has led to significantly more samples which need to be tested and probed.
Examples of automated processes which have greatly increased the number of samples which require analysis are combinatorial chemistry and parallel synthesis. Such methods are powerful techniques for increasing a chemist's productivity. It allows the chemist to produce large libraries of compounds relatively quickly. Prior to the advent of combinatorial chemistry and parallel synthesis, the process to discover new drugs had not changed significantly for over 100 years. Combinatorial chemistry and parallel synthesis changed forever the dogma that chemical entities should be synthesized, purified and analyzed one at a time. Combinatorial chemistry generates every possible variant, while parallel synthesis generates a subset for more intensive testing. In the parlance of the art, the phrase “combinatorial library” is often used to refer to a library of compounds generated to find and/or generate lead compounds, while the phrase “lead optimization library” is used to describe a library of compounds built around a previously identified lead compound.
In conventional combinatorial synthesis, compounds are conventionally synthesized on plastic beads that are segregated into different containers. In each container a different chemical building block is added to the beads. The beads from each container are then divided among a new set of containers and new building blocks added to each container. Once a lead series of compounds is identified in a combinatorial library, parallel synthesis is often employed. Parallel synthesis provides more flexibility in generating compounds. The chemistry may be performed using solid phase or solution phase chemistry.
Three common approaches are used in combinatorial organic synthesis. The first method employs arrays wherein synthesis is spatially addressable, building blocks being systematically reacted in individual reaction wells or positions to form separated discrete molecules. Active compounds are identified by their location in the array. A second technique, known as encoded mixture synthesis, uses inert chemical tags to identify each compound. The third approach, referred to as deconvolution, prepares a series of compound mixtures with each mixture being assayed, and the most active combination pursued. Such technique is typically employed in peptide optimization.
Typically in an array system, compositions are housed in either wells or in tubes, either of which are placed in a holding system or rack to generate a plurality of wells. The difficulty with using multi-well plates is that the scale of reactions can be limited due to the size of the wells, and it may be difficult to determine chemical yield as it is difficult to obtain the weight of individual samples in a plurality of wells. The use of multi-tube configurations, i.e., tubes to be placed within the well-rack locations, improves scale up of synthesis, but suffers from the disadvantage that error may be introduced if the tubes are misplaced in their well-rack locations.
Typically in combinatorial chemistry processes, a series of compounds are synthesized in multi-tube racks or multi-well plates. The location of each individual tube or well must be stored in a database handled by a computer system to allow association of the compounds with a particular position in the rack or well plate. After synthesis, the contents of each tube or well is generally transferred to a device for purification. Purification may be, for example, by means of a chromatographic device, such as a preparative scale HPLC, GC, preparatory supercritical fluid chromatography, or column chromatography. Various means are known in the art to identify compounds of interest when eluting from a column, including GC-MS, FID, NMR, ELSD, TLC, IR and UV. The solvent is then typically removed from each purified fraction, as, for example, by centrifugation or by vacuum oven, and the individual tubes weighed to gain information on percent yield. Thereafter, one or more chemical analyses are conventionally performed on the purified compounds, and the compounds are transferred to one or more multi-well plates or multi-tube racks for subsequent bioassay.
Multi-tube configurations in combinatorial arrays often include 48 or 96 tubes or more. Unfortunately, owing to lack of standardization, automated purification and chemical analysis equipment is not necessarily designed around the number of tubes in the multi-tube configurations used to prepare the compounds. The latter makes it quite difficult to track the identity and properties of compounds as they progress through stages of synthesis, purification and chemical analysis. In processing of the compositions housed within a tube, it is important to be able to identify precisely the location of the tube in the array.
Numerous methods have been employed in the tracking of tubes in combinatorial arrays. Probably the oldest known entails alphanumeric labeling of each tube. The problem with alphanumeric labeling is that once the labeled tube is dissociated from its known position within a bar coded rack, its previous identification is meaningless. Future identification is totally dependent on the storage database, and flawless retrieval from the storage system by robotics. Another of these methods entails placing a bar code on each tube in a multi-tube configuration. The bar codes permit one to keep track of the tubes, in particular to tubes that are moved to and from different multi-tube racks with varying numbers of tubes per rack. For example, MDS Panlabs produces a system that synthesizes compounds at a 1 mmole scale in multi-tube configurations in which each tube in the configuration is identified with a bar code, and is moved from stages of synthesis, purification and chemical analysis (typically including flow inject mass spectrometry) by means of robotic arms after the tube is optically read. Bar codes are typically attached using an adhesive, but could also be etched or otherwise affixed to the tubes.
As the size of many combinatorial libraries is great, it has been found in the art to be a tremendous burden to place, and keep track of, individual bar-codes on a plurality of tubes.
WO 00/47500 describes one process for overcoming such problem associated with the bar-coding of individual tubes. In such system, computer software is used to record the relative position of individual tubes, and the compounds within each tube, in a computer database. Automated means, by way of robotic arms, are used for transferring tubes from one multi-tube configuration to another with the position of the tubes in the first multi-tube configuration being correlated to the position of the tubes in the second multi-tube configuration. In short, instead of labeling each tube and monitoring the movement of each tube, the system employs relational database software which correlates the orientation of the tubes as a whole between more than one multi-rack.
The problem with the solution provided by WO 00/47500 is that for operation the system requires exact fidelity in the movement of the tubes between multi-racks. That is, it does not account for errors that may occur in movement, such as broken tubes, nor does it account for the desirability in many cases for analysis, such as bioassays, of certain samples to be halted with respect to one or more tubes due to factors such as poor purity or low sample size (e.g., the culling of samples from the whole). For example, if samples should fall from a rack during transport, there may be little to no possibility to positively identify the tube/sample without significant diagnostics. It also does not effectively deal with activities that result in the removal of tubes, such as microtubes, from the array, e.g., “cherry picking” of tubes, reformatting of tubes to compress storage, or culling of undesired tubes from a set (e.g., combichem post analytical). Further, because of the high fidelity requirement, the system employs expensive automated components that greatly increase the cost and complexity of the combinatorial chemistry analysis.
There is therefore the need for a simpler and cheaper system for assuring the identification of samples across processing, which allows for rapid visual verification of complete accuracy.